A basic mystery in developmental biology is how genes function to organize the growth and patterning of the developing embryo. In the fruit fly, Drosophila, genes have been identified which appear to function as developmental switches. A tissue which would normally follow one developmental pathway can be switched to another. Mutations in the genes can lead, for example, to flies with legs developing where the antennae would normally be. A cluster of such development-regulating genes, known as the Antennapedia Complex, has been extensively studied using genetic and developmental approaches. Recently, I have initiated an analysis of the molecular structure and function of the genes in the Complex. The genes have been purified as recombinant DNA. The proposed research is directed at understanding, at the molecular level, how the genes function to control development. We have begun to map genes and transcripts: sixteen mutations have been located on the physical map, and developmental stage-specific transcripts homologous to sections of the cloned DNA have been detected. The specific aims of the project are: 1) to align the physical and genetic maps by precisely mapping more breakpoints of mutations; 2) to locate and characterize each of the transcription units, 3) to identify proteins encoded by the genes, and to localize them in tissues and intracellularly; 4) to analyze the structure, and time and place of expression, of Antennapedia Complex-encoded gene products in mutant flies; 5) to isolate and characterize more mutations in the Complex; and 6) to use the recently developed technique for transforming fly embryos with DNA, and in vitro mutagenesis, to test the function of altered Antennapedia Complex genes in vivo.